Synthetic β-hydroxy ketone derivative inhibits cholinesterases, rescues oxidative stress and ameliorates cognitive deficits in 5XFAD mice model of AD

2020 ◽  
Vol 47 (12) ◽  
pp. 9553-9566
Author(s):  
Syed Ilyas Ahmad ◽  
Gowhar Ali ◽  
Tahir Muhammad ◽  
Rahim Ullah ◽  
Muhammad Naveed Umar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Deficits ◽  
Hydroxy Ketone ◽  
Mice Model ◽  
5Xfad Mice

scholarly journals 4-Hydroxynonenal Immunoreactivity Is Increased in the Frontal Cortex of 5XFAD Transgenic Mice

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 326
Author(s):  
Sang-Wook Shin ◽  
Dong-Hee Kim ◽  
Won Kyung Jeon ◽  
Jung-Soo Han
Keyword(s):  
Oxidative Stress ◽  
Frontal Cortex ◽  
Cognitive Deficits ◽  
Search Strategy ◽  
Learning Strategy ◽  
Maze Task ◽  
Spatial Search ◽  
Early Alzheimer’S Disease ◽  
5Xfad Mice ◽  
Switching Task

Oxidative stress was implicated in the functional impairment of the frontal cortex observed in early Alzheimer’s disease (AD). To elucidate this role in an animal AD model, we assessed cognitive function of 4-month-old five familial AD (5XFAD) transgenic (Tg) mice using a learning strategy-switching task requiring recruitment of the frontal cortex and measuring levels of 4-hydroxy-2-trans-nonenal (4-HNE), a marker of oxidative stress, in their frontal cortex. Mice were sequentially trained in cued/response and place/spatial versions of the water maze task for four days each. 5XFAD and non-Tg mice exhibited equal performance in cued/response training. However, 5XFAD mice used spatial search strategy less than non-Tg mice in the spatial/place training. Immunoblot and immunofluorescence staining showed that 4-HNE levels increased in the frontal cortex, but not in the hippocampus and striatum, of 5XFAD mice compared to those in non-Tg mice. We report early cognitive deficits related to the frontal cortex and the frontal cortex’s oxidative damage in 4-month-old 5XFAD mice. These results suggest that 4-month-old 5XFAD mice be a useful animal model for the early diagnosis and management of AD.

scholarly journals Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 630 ◽  
Author(s):  
Donald G Matthews ◽  
Maya Caruso ◽  
Charles F Murchison ◽  
Jennifer Y Zhu ◽  
Kirsten M Wright ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyloid Β ◽  
Water Extract ◽  
Centella Asiatica ◽  
Antioxidant Response ◽  
Plaque Burden ◽  
Heme Oxygenase 1 ◽  
Synaptic Density ◽  
Cognitive Benefits ◽  
5Xfad Mice

Centella asiatica (CA) herb is a traditional medicine, long reputed to provide cognitive benefits. We have reported that CA water extract (CAW) treatment improves cognitive function of aged Alzheimer’s disease (AD) model Tg2576 and wild-type (WT) mice, and induces an NRF2-regulated antioxidant response in aged WT mice. Here, CAW was administered to AD model 5XFAD female and male mice and WT littermates (age: 7.6 +/ − 0.6 months), and object recall and contextual fear memory were tested after three weeks treatment. CAW’s impact on amyloid-β plaque burden, and markers of neuronal oxidative stress and synaptic density, was assessed after five weeks treatment. CAW antioxidant activity was evaluated via nuclear transcription factor (erythroid-derived 2)-like 2 (NRF2) and NRF2-regulated antioxidant response element gene expression. Memory improvement in both genders and genotypes was associated with dose-dependent CAW treatment without affecting plaque burden, and marginally increased synaptic density markers in the hippocampus and prefrontal cortex. CAW treatment increased Nrf2 in hippocampus and other NRF2 targets (heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase catalytic subunit). Reduced plaque-associated SOD1, an indicator of oxidative stress, was observed in the hippocampi and cortices of CAW-treated 5XFAD mice. We postulate that CAW treatment leads to reduced oxidative stress, contributing to improved neuronal health and cognition.

Protective effect of citicoline against aluminum-induced cognitive impairments in rats

2016 ◽  
Vol 33 (4) ◽  
pp. 308-317 ◽  
Author(s):  
Ahmed O Abdel-Zaher ◽  
Mostafa M Hamdy ◽  
Mahran S Abdel-Rahman ◽  
Doaa H Abd El-hamid
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Passive Avoidance ◽  
Morris Water Maze ◽  
Cognitive Deficits ◽  
Aluminum Chloride ◽  
Water Maze ◽  
Cognitive Impairments ◽  
Radial Arm Maze ◽  
Time Required

The potential protective effect of citicoline on aluminum chloride-induced cognitive deficits was investigated in rats. In a Morris water maze, administration of aluminum chloride to rats for 90 days resulted in increased escape latency to reach the platform and decreased swimming speed in acquisition trials. Similarly, in probe trials, the time required to reach the hidden platform was increased and the time spent in the target quadrant was reduced. Also, administration of aluminum chloride to rats for 90 days increased the reference and working memory errors and time required to end the task in the radial arm maze. In addition, this treatment decreased the step-through latency in the passive avoidance test. Concurrently, treatment of rats with aluminum chloride for 90 days increased hippocampal glutamate, malondialdehyde, and nitrite levels and decreased intracellular reduced glutathione level. In the citicoline-treated group, aluminum chloride-induced learning and memory impairments as assessed by the Morris water maze, radial arm maze, and passive avoidance tests were inhibited. At the same time, treatment of rats with citicoline prevented the biochemical alterations induced by aluminum chloride in the hippocampus. It can be concluded that elevation of hippocampal glutamate level with consequent oxidative stress and nitric oxide (NO) overproduction may play an important role in aluminum-induced cognitive impairments. Also, our results suggest, for the first time, that citicoline can protect against the development of these cognitive deficits through inhibition of aluminum-induced elevation of glutamate level, oxidative stress, and NO overproduction in the hippocampus.

Tetraclinis articulata essential oil mitigates cognitive deficits and brain oxidative stress in an Alzheimer's disease amyloidosis model

Phytomedicine ◽  
2019 ◽  
Vol 56 ◽  
pp. 57-63 ◽  
Author(s):  
Fatima Zahra Sadiki ◽  
Mostafa El Idrissi ◽  
Oana Cioanca ◽  
Adriana Trifan ◽  
Monica Hancianu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Essential Oil ◽  
Cognitive Deficits ◽  
Tetraclinis Articulata ◽  
Brain Oxidative Stress

scholarly journals An ultra-low dose of ∆9-tetrahydrocannabinol improves Alzheimer's Disease-related cognitive deficits

2021 ◽  
Author(s):  
keren nitzan ◽  
Leah Ellenbogen ◽  
Tal Beniamin ◽  
Yosef Sarne ◽  
Ravid Doron
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Low Dose ◽  
Brain Injuries ◽  
Single Injection ◽  
Pharmaceutical Preparation ◽  
Sirtuin 1 ◽  
Mice Model ◽  
High Doses ◽  
5Xfad Mice

Alzheimer's disease (AD) is the most common form of dementia. AD has a physical, emotional, and economic impact on the patients and their families and society at large. More than a decade since its discovery, there is still no available treatment. Delta-9-Tetrahydrocannabinol (THC) is emerging as a promising therapeutic agent. Using THC in conventional-high doses may have deleterious effects. Therefore, we propose to use an ultra-low dose of THC (ULD-THC). We previously published that a single injection of ULD-THC elevated Sirtuin-1 (Sirt-1) levels in the brain and ameliorated cognitive functioning in several models of brain injuries as well as in naturally aging mice. Our working hypothesis suggests that ULD-THC can prevent and even reverse AD pathology. In this preliminary study, we saw that a single injection of ULD-THC alleviated cognitive impairments in a mice model of AD, 5xFAD mice. Our work may establish the foundations for the development of a pharmaceutical preparation for the treatment of AD patients, thus, bringing the ULD-THC treatment closer to clinical application.

scholarly journals Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhong-he Liu ◽  
Hong-guang Chen ◽  
Pan-feng Wu ◽  
Qing Yao ◽  
Hong-ke Cheng ◽  
...  
Keyword(s):  
Body Weight ◽  
Cerebral Cortex ◽  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Ache Activity ◽  
Memory Deficits ◽  
Test Body ◽  
Morris Water Maze Test ◽  
Diabetic Mice ◽  
Mice Model

Objective. The effects of Flos Puerariae extract (FPE) on cognitive impairment associated with diabetes were assessed in C57BL/6J mice.Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ) for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA) and total cholesterol (TCH) in serum, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and acetylcholinesterase (AChE) activities in cerebral cortex and hippocampus were also measured.Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE.Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

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